The in vivo antitumor effects on human COLO 205 cancer cells of the 4,7-dimethoxy-5-(2-propen-1-yl)-1,3-benzodioxole (apiole) derivative of 5-substituted 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) isolated from the fruiting body of Antrodia camphorate
Po-Li Wei1, Shih-Hsin Tu2, Hsiu-Man Lien3, Li-Ching Chen4, Ching-Shyang Chen1, Chih-Hsiung Wu5, Ching-Shui Huang2, Hui-Wen Chang6, Chien-Hsi Chang6, How Tseng7, Yuan-Soon Ho8
1 Department of Surgery, School of Medicine, Taipei Medical University, Taipei, Taiwan
2 Department of Surgery, School of Medicine; Graduate Institute of Medical Sciences, Taipei Medical University; Department of Surgery, Cathay General Hospital, Taipei, Taiwan
3 Department of Chemistry, Tunghai University, Taichung, Taiwan
4 Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
5 Department of Surgery, School of Medicine, Taipei Medical University; Department of Surgery, Taipei Medical University-Shuang Ho Hospital; Center of Excellence for Cancer Research, Taipei, Taiwan
6 Department of Laboratory Medicine, Taipei Medical University, Taipei, Taiwan
7 Graduate Institute of Medical Sciences; Department of Biochemistry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
8 Center of Excellence for Cancer Research; Department of Laboratory Medicine; School of Medical Laboratory Science and Biotechnology, College of Medicine, Taipei Medical University, Taipei, Taiwan
Graduate Institute of Biomedical Technology, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 110
Source of Support: This study was supported by National Science Council grants NSC 95-2320-B-038-016-MY3 and DOH100-TD-C-111-008 to Dr. Ho and grant NSC 96-2314-B-038-002 to Dr. Wu.,, Conflict of Interest: None
Context: The compound 4,7-dimethoxy-5-(2-propen-1-yl)-1,3-benzodioxole (apiole) has been isolated from several different plant species, including Petroselinum sativum. Our recent study found that apiole is a chemical derivative of 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1), which has been isolated from dried Antrodia camphorata (AC ) fruiting bodies, a traditional Chinese medicine with antitumor properties.
Aims: Our previous in vitro study demonstrated that apiole inhibits the growth of human colon (COLO 205) cancer cells through the arrest of the cell cycle in G0/G1 phase. The in vivo antitumor effects of apiole were evaluated in this study.
Setting and Design: Apiole was administered to mice at 1-30 mg/kg body weight through intraperitoneal (I.P.) injection three times per week (defined as a dosage of 1×-30×).
Materials and Methods: The in vivo antitumor effects of apiole were evaluated in mice with xenografts of COLO 205 cells.
Statistical Analysis: All of the data are reported as the means ± S.E. Comparisons were performed with a one-way analysis of variance (ANOVA) followed by a Fisher's least significant difference test. Significance was defined as P < 0.05.
Results: Apiole (> 1×) markedly decreased the growth of COLO 205 human colon cancer cell tumor xenografts in an athymic nude mouse model system through the up-regulation of cell cycle regulators, such as p53, p21/Cip1, and p27/Kip1. The apiole-induced increase in G0/G1 phase cell cycle regulators was also associated with a significant decrease in the expression of cyclins D1 and D3. Surprisingly, statistically significantly higher tumor volumes were observed in mice that received 5× apiole compared with 30× apiole-treated mice (P < 0.05). No gross signs of toxicity were observed (e.g., body weight changes, general appearance, or individual organ effects) in any group.
Conclusions: Our results show, for the first time, the promising antitumor effects of apiole against colon tumors in an in vivo xenograft model.